Lisa Orme

Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer.

We conducted a phase 1 study of 9 pediatric patients with recurrent brain tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce antitumor vaccine (DCRNA) preparations. The objectives of this study included (1) establishing safety and feasibility and (2) measuring changes in general, antigen-specific, and tumor-specific immune responses after DCRNA. Dendritic cells were derived from freshly isolated monocytes after 7 days of culture with IL-4 and granulocyte-macrophage colony-stimulating factor, pulsed with autologous tumor RNA, and then cryopreserved. Patients received at least 3 vaccines, each consisting of an intravenous and an intradermal administration at biweekly intervals. The study showed that this method for producing and administering DCRNA from a single leukapheresis product was both feasible and safe in this pediatric brain tumor population. Immune function at the time of enrollment into the study was impaired in all patients tested. While humoral responses to recall antigens (diphtheria and tetanus) were intact in all patients, cellular responses to mitogen and recall antigens were below normal. Following DCRNA vaccine, 2 of 7 patients showed stable clinical disease and 1 of 7 showed a partial response. Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA. This study showed that DCRNA vaccines are both safe and feasible in children with tumors of the central nervous system with a single leukapheresis.

Results of a Phase I study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children with stage 4 neuroblastoma

A Phase I study of 11 pediatric patients with newly diagnosed, Stage 4 neuroblastoma was conducted using monocyte‐derived dendritic cells (DC) pulsed with tumor RNA to produce antitumor vaccines (DCRNA).

Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression

Despite the widespread use of megestrol acetate (MA) among a growing number of pediatric oncology departments, there is only one published study on the use of MA in children with malignant disease. The objectives of the current study were to examine the effect of MA in improving the nutritional status of children with malignant disease and to describe and consider the implications of MA‐associated adrenal suppression that was found consistently.

Biallelic pms2 Mutations and a Distinctive Childhood Cancer Syndrome

Biallelic mutations in PMS2, a gene usually associated in heterozygous form with hereditary nonpolyposis colorectal cancer (HNPCC), results in a recently described childhood cancer syndrome. The tumor spectrum encompasses atypical brain cancers, hematologic malignancies, and colonic polyposis and cancer. Cutaneous stigmata resembling café-au-lait macules with more diffuse margins are frequently seen. Onset is as young as 2 years. The risk of second malignancy is high. Evidence exists for surveillance for bowel cancer, but surveillance for the wider tumor spectrum is of uncertain benefit. We report a consanguineous Australian-Lebanese family with multiple affected individuals shown to be homozygous for a PMS2 exon 7 deletion. We also review published cases of biallelic mutations in HNPCC-related genes. Early recognition of this familial cancer syndrome is critical, and should prompt investigation for familial HNPCC mutations.

Creating a Global Community of Practice for Oncofertility

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Youth Cancer Services in Australia: Development and Implementation. International Perspectives on AYAO, Part 3

Based on an increased appreciation of the unique challenges facing adolescents and young adults with cancer, there has been a coordinated national effort in Australia in recent years to address this issue. In 2007, CanTeen, a consumer support organization for young people with cancer, partnered with the Australian federal government to fund the development of a network of multidisciplinary Youth Cancer Services across the country. This has resulted in a collaborative effort involving clinicians, the federal and state governments, consumers, CanTeen, and other non-government organizations to implement equitable and sustainable models of care that will improve the coordination of services, treatment, and support for 15-25-year-olds with cancer. The aims of this article are to outline the origins of Youth Cancer Services in Australia, to discuss several innovative models of care that have developed according to local geographic and demographic need, to highlight some successful strategies and early obstacles to service development, and to outline the challenges for the future.

Outpatient Versus Inpatient IV Antibiotic Management for Pediatric Oncology Patients With Low Risk Febrile Neutropenia: A Randomised Trial

Febrile neutropenia (FN) is a frequent, serious complication of intensive pediatric chemotherapy regimens. The aim of this trial was to compare quality of life (QOL) between inpatient and outpatient intravenous antibiotic management of children and adolescents with low risk febrile neutropenia (LRFN).

Reproductive concerns of children and adolescents with cancer: challenges and potential solutions

The diagnosis of a potentially life-threatening cancer is one of the most traumatic events that can befall a young person and his or her family. However, fortunately, most young people will survive their cancer and its treatment and go on to lead a long and healthy life, with an appropriate expectation of being able to have their own genetic family. However, cancer treatment, including surgery, chemotherapy, and radiotherapy, can have temporary and permanent effects on fertility, including damage to the uterus and pituitary gland, and reduction, or obliteration, of gonadal function, with consequential loss of oocytes or spermatozoa, which may result in ovarian or testicular failure. As the gamete pool is nonrenewable, permanent gonadal failure precludes subsequent fertility with a patients own genetic material. Awareness and acknowledgement of the likely future fertility implications of cancer treatment is an essential part of any discussion about proposed therapies. Options for girls and young women include freezing mature oocytes and ovarian tissue, as well as attempting to protect the ovaries from the gonadotoxic effects of treatment. Options for boys and young men include semen collection and storage as well as testicular biopsy with freezing of testicular tissue or spermatozoa retrieved from the tissue. Fertility options can now be offered with increasing optimism about success and the provision of a genuine opportunity for having a family. While the initiation of cancer treatment is sometimes truly urgent, the opportunity for a detailed discussion about implications for fertility is of paramount importance for patients and their families and provides both reassurance and optimism about the future.

A short report on current fertility preservation strategies for boys

Advances in cancer treatment have led to improved long‐term survival after childhood cancer, but often at a price of impaired future fertility. Fertility preservation (FP) in male children and early adolescents poses unique challenges as efficacy is unproven.

Inconsistencies and time delays in site-specific research approvals hinder collaborative clinical research in Australia

The aim of this study was to describe the time and documentation needed to gain ethics and governance approvals in Australian states with and without a centralised ethical review system.